The object of this research is to study, in in vitro systems established in this laboratory and in an appropriate animal tumor model, some of the phenomena pertaining to cell differentiation, tumor maturation and stroma-induction, as expressed morphologically, biochemically and immunologically, in neoplasms of the central and peripheral nervous system. The tumors investigated include human neoplasms; experimental rat tumors obtained following transplacental ethylnitrosourea (ENU); an established glial rat tumor cell line (C-6); and the neuroepithelial component of a transplantable mouse testicular teratoma (OTT-6050) maintained in syngeneic animals in ascitic and in solid forms. Two main approaches are used: 1) The establishment of suitable organotypic in vitro systems that permit the sequential study of differentiation by morphological, immunological and immunoradiometric methods; 2) the biological properties and in vivo and in vitro behavior and manipulation of the mouse transplantable teratoma as a model for neuroepithelial neoplastic differentiation. The interest of this model lies in its applicability to the study of embryonal central nervous system tumors in man. A long-term objective is the production of a pure experimental tumor in which differentiation is restricted to neuroepithelial derivatives. Special markers of differentiation include those specific for neuroepithelial cells, those concerned with gliofibrillogenesis (GFA protein), melanin production in primitive neuroepithelium, and the demonstration and measurement of neurotransmitter substances and the enzymes concerned with their synthesis and degradation. Kinetic systems on such in vitro systems are designed to establish correlations between the synthesis of antigenic determinants, nucleic acid synthetic processes, and phases of the cell cycle.